[Mortality associated with neurocognitive disorder and dependence in people over 55 years of age. Systematic review]. / Mortalidad asociada al trastorno neurocognitivo y dependencia en personas mayores de 55 años. Revisión sistemática.

INTRODUCTION: The increasing aging of the population brings with it an increase in the incidence of neurocognitive disorder (NCD) as well as various situations that generate dependence. OBJECTIVE: To analyze by means of a systematic review the relationship between NCD and dependence with the risk of mortality in the elderly. METHODS: A bibliographic search of longitudinal studies published in Pubmed and Scopus addressing the relationship between NCI, dependence for basic activities of daily living (ADL) and mortality published between 1995 and 2021 was performed. Of the 1040 articles found, 10 studies were selected. RESULTS: It was observed that cohorts of elderly people with NCI presented mortality risk associated with ABVD impairment (Barthel test) and Mini-Mental State Examination scores following a significant linear trend. Other factors associated with mortality risk were low levels of education, living alone, and frailty. CONCLUSIONS: The results underline the importance of performing assessments of cognitive and functional status using validated scales, since both areas are associated with mortality. The link between the three terms used in the search for this work is clear, but it is noteworthy that there are few longitudinal studies that analyze them together. The assessment of dependence and cognitive function in older adults should be considered in both research and clinical practice as it would provide information on their possible relationship with mortality.

99mTc-Labeled Cyclic Peptide Targeting PD-L1 as a Novel Nuclear Imaging Probe.

Recent cancer therapies have focused on reducing immune suppression in the tumor microenvironment to prevent cancer progression and metastasis. PD-1 is a checkpoint protein that stops the immune response and is expressed on immune T cells. Cancer cells express a PD-1 ligand (PD-L1) to bind to the T-cell surface and activate immunosuppressive pathways. This study aimed to design, synthesize, and evaluate a 99mTc-labeled PD-L1-targeting cyclic peptide inhibitor (99mTc-iPD-L1) as a novel SPECT radiopharmaceutical for PD-L1 expression imaging. AutoDock software (version 1.5) was used to perform molecular docking for affinity calculations. The chemical synthesis was based on the coupling reaction of 6-hydrazinylpyridine-3-carboxylic acid with a 14-amino-acid cyclic peptide. iPD-L1 was prepared for 99mTc labeling. Radio-HPLC was used to verify radiochemical purity. The stability of the radiopeptide in human serum was evaluated by HPLC. iPD-L1 specificity was assessed by SDS-PAGE. [99mTc]Tc-iPD-L1 cellular uptake in PD-L1-positive cancer cells (HCC827 and HCT116) and biodistribution in mice with induced tumors were also performed. One patient with advanced plantar malignant melanoma received [99mTc]Tc-iPD-L1. The iPD-L1 ligand (AutoDock affinity: -6.7 kcal/mol), characterized by UPLC mass, FT-IR, and UV-Vis spectroscopy, was obtained with a chemical purity of 97%. The [99mTc]Tc-iPD-L1 was prepared with a radiochemical purity of >90%. In vitro and in vivo analyses demonstrated [99mTc]Tc-iPD-L1 stability (>90% at 24 h) in human serum, specific recognition for PD-L1, high uptake by the tumor (6.98 ± 0.89% ID/g at 1 h), and rapid hepatobiliary and kidney elimination. [99mTc]Tc-iPD-L1 successfully detected PD-L1-positive lesions in a patient with plantar malignant melanoma. The results obtained in this study warrant further dosimetric and clinical studies to determine the sensitivity and specificity of [99mTc]Tc-iPD-L1/SPECT for PD-L1 expression imaging.

Increase in Vascular Function Parameters According to Lifestyles in a Spanish Population without Previous Cardiovascular Disease-EVA Follow-Up Study.

The aim of this longitudinal descriptive observational study was to analyze the influence of different lifestyles on arterial stiffness (AS) throughout five years of follow-up and to describe the differences by sex in a Spanish adult population without cardiovascular disease at the start of the study. A random stratified sampling by age and sex was used to obtain 501 subjects included in the initial assessment. No cardiovascular disease was allowed in the subjects. The average age was 55.9 years, and 50.3% were women. A total of 480 subjects were analyzed again five years later. Alcohol and tobacco consumption were collected with standardized questionnaires. Adherence to the Mediterranean diet was assessed with the Mediterranean diet adherence screener (MEDAS) questionnaire. Physical activity was assessed with the short version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF) and sedentary time was assessed with the Marshall Sitting Questionnaire (MSQ). AS was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central augmentation index (CAIx) with SphygmoCor System®, and ankle pulse wave velocity (baPWV) and cardio ankle vascular index (CAVI) with Vasera VS-1500®. Increases in vascular function measures per year of follow-up were: cfPWV = 0.228 ± 0.360 m/s, baPWV = 0.186 ± 0.308 m/s, CAVI = 0.041 ± 0.181 m/s, and CAIx = 0.387 ± 2.664 m/s. In multiple regression analysis, positive association was shown between an increase in baPWV and tobacco index (ß = 0.007) and alcohol consumption (ß = 0.005). Negative association was shown between CAVI and Mediterranean diet score (ß = -0.051). In multinomial logistic regression analysis, the OR of tobacco index of subjects with a cfPWV increase >P75 was OR = 1.025 and of subjects classified between P25 and P75 was OR = 1.026 regarding subjects classified with an increase P75 was OR = 1.006 regarding subjects classified with an increase P75, and an OR = 0.841 was found of subjects classified between P25-75 regarding subjects classified with an increase

The state of art of awake craniotomy in Latin American countries: a scoping review.

BACKGROUND AND OBJECTIVE: Awake craniotomy (AC) is a valuable technique for surgical interventions in eloquent areas, but its adoption in low- and middle-income countries faces challenges like limited infrastructure, trained personnel shortage, and inadequate funding. This scoping review explores AC techniques in Latin American countries, focusing on patient characteristics, tumor location, symptomatology, and outcomes. METHODS: A scoping review followed PRISMA guidelines, searching five databases in English, Spanish, and Portuguese. We included 28 studies with 258 patients (mean age: 43, range: 11-92). Patterns in AC use in Latin America were analyzed. RESULTS: Most studies were from Brazil and Mexico (53.6%) and public institutions (70%). Low-grade gliomas were the most common lesions (55%), most of them located in the left hemisphere (52.3%) and frontal lobe (52.3%). Gross-total resection was achieved in 34.3% of cases. 62.9% used an Asleep-Awake-Asleep protocol, and 14.8% used Awake-Awake-Awake. The main complication was seizures (14.6%). Mean post-surgery discharge time was 68 h. Challenges included limited training, infrastructure, and instrumentation availability. Strategies discussed involve training in specialized centers, seeking sponsorships, applying for awards, and multidisciplinary collaborations with neuropsychology. CONCLUSION: Improved accessibility to resources, infrastructure, and adequate instrumentation is crucial for wider AC availability in Latin America. Despite disparities, AC implementation with proper training and teamwork yields favorable outcomes in resource-limited centers. Efforts should focus on addressing challenges and promoting equitable access to this valuable surgical technique in the region.

Lifestyles, arterial aging, and its relationship with the intestinal and oral microbiota (MIVAS III study): a research protocol for a cross-sectional multicenter study.

Background: The microbiota is increasingly recognized as a significant factor in the pathophysiology of many diseases, including cardiometabolic diseases, with lifestyles probably exerting the greatest influence on the composition of the human microbiome. The main objectives of the study are to analyze the association of lifestyles (diet, physical activity, tobacco, and alcohol) with the gut and oral microbiota, arterial aging, and cognitive function in subjects without cardiovascular disease in the Iberian Peninsula. In addition, the study will examine the mediating role of the microbiome in mediating the association between lifestyles and arterial aging as well as cognitive function. Methods and analysis: MIVAS III is a multicenter cross-sectional study that will take place in the Iberian Peninsula. One thousand subjects aged between 45 and 74 years without cardiovascular disease will be selected. The main variables are demographic information, anthropometric measurements, and habits (tobacco and alcohol). Dietary patterns will be assessed using a frequency consumption questionnaire (FFQ) and the Mediterranean diet adherence questionnaire. Physical activity levels will be evaluated using the International Physical Activity Questionnaire (IPAQ), Marshall Questionnaire, and an Accelerometer (Actigraph). Body composition will be measured using the Inbody 230 impedance meter. Arterial aging will be assessed through various means, including measuring medium intimate carotid thickness using the Sonosite Micromax, conducting analysis with pulse wave velocity (PWA), and measuring pulse wave velocity (cf-PWV) using the Sphygmocor System. Additional cardiovascular indicators such as Cardio Ankle Vascular Index (CAVI), ba-PWV, and ankle-brachial index (Vasera VS-2000®) will also be examined. The study will analyze the intestinal microbiota using the OMNIgene GUT kit (OMR-200) and profile the microbiome through massive sequencing of the 16S rRNA gene. Linear discriminant analysis (LDA), effect size (LEfSe), and compositional analysis, such as ANCOM-BC, will be used to identify differentially abundant taxa between groups. After rarefying the samples, further analyses will be conducted using MicrobiomeAnalyst and R v.4.2.1 software. These analyses will include various aspects, such as assessing α and ß diversity, conducting abundance profiling, and performing clustering analysis. Discussion: Lifestyle acts as a modifier of microbiota composition. However, there are no conclusive results demonstrating the mediating effect of the microbiota in the relationship between lifestyles and cardiovascular diseases. Understanding this relationship may facilitate the implementation of strategies for improving population health by modifying the gut and oral microbiota. Trial registration: clinicaltrials.gov/ct2/show/NCT04924907, ClinicalTrials.gov, identifier: NCT04924907. Registered on 21 April 2021.

Long-term Effectiveness of a Smartphone App Combined With a Smart Band on Weight Loss, Physical Activity, and Caloric Intake in a Population With Overweight and Obesity (Evident 3 Study): Randomized Controlled Trial.

BACKGROUND: Multicomponent mobile health approaches can improve lifestyle intervention results, although little is known about their long-term effectiveness. OBJECTIVE: This study aims to evaluate the long-term effectiveness (12 months) of a multicomponent mobile health intervention-combining a smartphone app, an activity tracker wristband, and brief counseling, compared with a brief counseling group only-on weight loss and improving body composition, physical activity, and caloric intake in Spanish sedentary adults with overweight or obesity. METHODS: We conducted a randomized controlled, multicenter clinical trial (Evident 3). A total of 650 participants were recruited from 5 primary care centers, with 318 participants in the intervention group (IG) and 332 in the control group (CG). All participants were briefly counseled about a healthy diet and physical activity at the baseline visit. For the 3-month intervention period, the IG received training to use the app to promote healthy lifestyles and the smart band (Mi Band 2, Xiaomi). All measurements were performed at baseline and at 3 and 12 months. Physical activity was measured using the International Physical Activity Questionnaire-Short Form. Nutritional habits were assessed using the Food Frequency Questionnaire and Adherence to Mediterranean diet questionnaire. RESULTS: Of the 650 participants included, 563 (86.6%) completed the 3-month visit and 443 (68.2%) completed the 12-month visit. After 12 months, the IG showed net differences in weight (-0.26, 95% CI -1.21 to 0.70 kg; P=.02), BMI (-0.06, 95% CI -0.41 to 0.28 points; P=.01), waist-height ratio (-0.25, 95% CI -0.94 to 0.44; P=.03), body adiposity index (-0.33, 95% CI -0.77 to 0.11; P=.03), waist circumference (-0.48, 95% CI -1.62 to 0.66 cm, P=.04) and hip circumference (-0.69, 95% CI -1.62 to 0.25 cm; P=.03). Both groups lowered daily caloric intake and increased adherence to the Mediterranean diet, with no differences between the groups. The IG increased light physical activity time (32.6, 95% CI -30.3 to 95.04 min/week; P=.02) compared with the CG. Analyses by subgroup showed changes in body composition variables in women, people aged >50 years, and married people. CONCLUSIONS: The low-intensity intervention of the Evident 3 study showed, in the IG, benefits in weight loss, some body composition variables, and time spent in light physical activity compared with the CG at 3 months, but once the devices were collected, the downward trend was not maintained at the 12-month follow-up. No differences in nutritional outcomes were observed between the groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03175614; https://clinicaltrials.gov/ct2/show/NCT03175614. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1097/MD.0000000000009633.

Effect of a Multicomponent mHealth Intervention on the Composition of Diet in a Population with Overweight and Obesity-Randomized Clinical Trial EVIDENT 3.

A balanced diet can help in the prevention of chronic diseases. The aim of this study was to evaluate the effect of an mHealth intervention on the distribution of macronutrients and the intake of food groups. A total of 650 participants were included in this multi-center, clinical, randomized, controlled trial (Evident 3 study). All participants were given brief advice about diet and exercise. The intervention group received, in addition, an app (Evident 3) for the self-recording of their diet and an activity tracker wristband for 3 months. Follow-up visits were performed at 3 and 12 months to collect the diet composition using the Food Frequency Questionnaire. There were decreases in the intake of total calories, fat, protein and carbohydrates in both groups throughout the study, without significant differences between them. The intervention group reduced the intake of cholesterol (-30.8; 95% CI -59.9, -1.7) and full-fat dairies (-23.3; 95% CI -42.8, -3.8) and increased the intake of wholemeal bread (3.3; 95% CI -6.7, 13.3) and whole-grain cereals (3.4; 95% CI -6.8, 13.7) with respect to the control group. No differences were found in the rest of the nutritional parameters. The brief advice is useful to promote a healthier diet, and the app can be a support tool to obtain changes in relevant foods, such as integral foods, and the intake of cholesterol. Trial registration: ClinicalTrials.gov with identifier NCT03175614.

Effects of cocoa-rich chocolate on cognitive performance in postmenopausal women. A randomised clinical trial.

OBJECTIVES: The aim of this research was to evaluate the effects of adding 10 g of cocoa-rich chocolate (99%) to the habitual diet on cognitive performance in postmenopausal women. METHODS: Following a randomised controlled parallel clinical trial, a total of 140 postmenopausal women aged 50-64 were recruited. The intervention group (n = 73) consumed daily 10 g of chocolate (99% cocoa) in addition to their usual food intake for 6 months, whereas the control group (n = 67) did not receive any intervention. Attention and executive functions, verbal memory, working memory, phonological fluency, category fluency and clinical variables were assessed at baseline and 6 months. RESULTS: Trail Making Test B execution time showed a decreased of -12.08 s (95% CI: -23.99, -0.18; p = 0.047) in the intervention group compared to the control group, after adjusting for age, educational level, time elapsed from the beginning of menopause and daily energy consumption (Cohen's d = -0.343). Attention, immediate or delayed verbal memory, phonological or category fluency, and working memory remained unchanged. CONCLUSIONS: The consumption of cocoa-rich (99%) chocolate in addition to the habitual diet could be related to a slight improvement in cognitive performance regarding cognitive flexibility and processing speed in postmenopausal women, with no changes in the rest of the cognitive performance variables evaluated.Trial registration: This clinical trial has been registered at clinicaltrials.gov as NCT03492983.

Vascular target organ damage in patients with Philadelphia negative myeloproliferative syndrome: A propensity score analysis.

PURPOSE: To assess whether subjects with Philadelphia negative myeloproliferative neoplasms (Ph-MPNs) show differences in the presence of vascular, cardiac or renal target organ damage (TOD) and other vascular function parameters as compared to individuals without this condition. METHODS: An observational study was conducted. Fifty-seven subjects diagnosed with Ph-MPNs used as cases and 114 subjects without Ph-MPNs as controls. We matched the subjects with and without Ph-MPNs using the propensity scores in a 1:2 ratio using the variables gender, type 2 diabetes mellitus, high blood pressure, hyperlipidaemia and smoking. Vascular, cardiac and renal TOD were established according to the criteria of the European Society of Hypertension and Cardiology guidelines. Arterial stiffness was also assessed using the cardio-ankle vascular index (CAVI). RESULTS: Mean age was 63.50±11.70 and 62.90±8.32 years in subjects with and without Ph-MPNs, 32 females (56%) in the first group and 62 (54%) in the second. Subjects with Ph-MPNs have a higher percentage of carotid injury than subjects without Ph-MPNs (35.1% vs. 21.1%) and higher albumin/creatinine ratio. In the logistic regression analysis, subjects with Ph-MPNs had an OR=2.382 (IC95% 1.066-5.323) for carotid injury versus those without haematological disease. CONCLUSIONS: Subjects with Ph-MPNs have twice the risk of by carotid injury than those without haematological disease.

Cocoa-rich chocolate and body composition in postmenopausal women: a randomised clinical trial.

During menopause, women undergo a series of physiological changes that include a redistribution of fat tissue. This study was designed to investigate the effect of adding 10 g of cocoa-rich chocolate to the habitual diet of postmenopausal women daily on body composition. We conducted a 6-month, two-arm randomised, controlled trial. Postmenopausal women (57·2 (sd 3·6) years, n 132) were recruited in primary care clinics. Participants in the control group (CG) did not receive any intervention. Those of the intervention group (IG) received 10 g daily of 99 % cocoa chocolate in addition to their habitual diet for 6 months. This quantity comprises 247 kJ (59 kcal) and 65·4 mg of polyphenols. The primary outcomes were the between-group differences in body composition variables, measured by impendancemetry at the end of the study. The main effect of the intervention showed a favourable reduction in the IG with respect to the CG in body fat mass (-0·63 kg (95 % CI -1·15, -0·11), P = 0·019; Cohen's d = -0·450) and body fat percentage (-0·79 % (95 % CI -1·31, -0·26), P = 0·004; Cohen's d = -0·539). A non-significant decrease was also observed in BMI (-0·20 kg/m2 (95 % CI -0·44, 0·03), P = 0·092; Cohen's d = -0·345). Both the body fat mass and the body fat percentage showed a decrease in the IG for the three body segments analysed (trunk, arms and legs). Daily addition of 10 g of cocoa-rich chocolate to the habitual diet of postmenopausal women reduces their body fat mass and body fat percentage without modifying their weight.

Seroprevalencia de anticuerpos anti-Leptospira spp. en estudiantes de Medicina Veterinaria y Zootecnia de la Costa Grande de Guerrero, México / Seroprevalence of anti-Leptospira spp. antibodies among Veterinary Medicine and Zootechnics students from Costa Grande of Guerrero, Mexico

Introducción: La leptospirosis humana es una enfermedad zoonótica con manifestaciones clínicas inespecíficas (cefalea y mialgia), las cuales pueden confundirse con otras enfermedades febriles como: gripe, malaria, dengue, fiebre amarilla, hepatitis vírica y rickettsiosis. Objetivo: Determinar la prevalencia de anticuerpos anti-Leptospira en estudiantes de la carrera de Medicina Veterinaria y Zootecnia de la Costa Grande de Guerrero. Métodos: Se aplicó un cuestionario a los estudiantes de la Escuela Superior de Medicina Veterinaria y Zootecnia No. 3 con la finalidad de conocer algunos factores de riesgo asociados a la presencia de anticuerpos anti-Leptospira spp. La determinación de anticuerpos anti-Leptospira y la identificación de las serovariedades se realizaron con la técnica de microaglutinación. Se consideró un suero positivo cuando se observó una aglutinación en una dilución igual o mayor a 1:100. Resultados: En el estudio la seroprevalencia de anticuerpos anti-Leptospira spp. fue de 12,1 por ciento (8/66). Se detectaron anticuerpos a 8 serovariedades de Leptospira spp. El 62,5 por ciento (5/8) de los sueros presentó más de una serovariedad. Las serovariedades y frecuencia fueron icterohaemorrhagiae 25 por ciento (4/16), hardjo 18,8 por ciento (3/16), pyrogenes 18,8 por ciento (3/16), pomona 12,5 por ciento (2/16), canicola 6,2 por ciento (1/16) wolffi 6,2 por ciento (1/16) tarassovi 6,2 por ciento (1/16) y bratislava 6,2 por ciento (1/16). Los factores de riesgo estudiados no se relacionaron con la presencia de anticuerpos anti-Leptospira. Conclusiones: En el presente estudio se encontraron anticuerpos a Leptospira spp. en estudiantes de Medicina Veterinaria y Zootecnia. Por tanto, es pertinente proporcionar información a los estudiantes para prevenir el contacto con el agente causal de la leptospirosis(AU)

Introduction: Human leptospirosis is a zoonotic disease of unspecific clinical manifestations (headache and myalgia) which may be confused with those of other febrile diseases, such as influenza, malaria, dengue, yellow fever, viral hepatitis and rickettsiosis. Objective: Determine the prevalence of anti-Leptospira antibodies among Veterinary Medicine and Zootechnics students from Costa Grande de Guerrero. Methods: A questionnaire was applied to students from the Higher Education Veterinary Medicine and Zootechnics School No. 3 to obtain information about risk factors associated to the presence of anti-Leptospira spp. antibodies. Microagglutination technique was used to determine anti-Leptospira antibodies and identify serovars. A serum sample was considered positive when agglutination was observed at a dilution equal to or greater than 1:100. Results: Seroprevalence of anti-Leptospira spp. antibodies was found to be 12.1 percent (8/66). Antibodies were detected for 8 serovars of Leptospira spp. Of the serum samples analyzed, 62.5 percent (5/8) contained more than one serovar. The serovars and their frequency were the following: icterohaemorrhagiae 25 percent (4/16), hardjo 18.8 percent (3/16), pyrogenes 18.8 percent (3/16), pomona 12.5 percent (2/16), canicola 6.2 percent (1/16), wolffi 6.2 percent (1/16), tarassovi 6.2 percent (1/16) and bratislava 6.2 percent (1/16). The risk factors studied were not related to the presence of anti-Leptospira antibodies. Conclusions: Leptospira spp. antibodies were found in Veterinary Medicine and Zootechnics students. It is therefore advisable to provide students with the information required to prevent contact with the causative agent of leptospirosis(AU)

The Relationship Between Alcohol Consumption With Vascular Structure and Arterial Stiffness in the Spanish Population: EVA Study.

BACKGROUND: Controversy exists regarding the way alcohol use is associated with vascular structure and arterial stiffness parameters. The purpose of this study is to evaluate the association between alcohol consumption with vascular structure and arterial stiffness in an adult population. METHODS: We conducted a cross-sectional study. Five hundred and one participants were recruited by random sampling from an urban population of 43,946 individuals aged 35 to 75 years, assigned from 5 healthcare centers located in Salamanca, Spain. This was a subanalysis of the EVA study. Arterial stiffness was assessed by measuring cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (ba-PWV) with the VaSera VS-1500® device, and carotid-femoral pulse wave velocity (cf-PWV) with the Sphygmocor® . Vascular structure was evaluated by measuring the carotid intima-media thickness (c-IMT) with a Sonosite Micromax® ultrasound. Alcohol consumption was calculated using a standardized questionnaire and quantified in g/wk. RESULTS: In the multiple regression analysis adjusted for sex, age, smoking status, and systolic blood pressure, the c-IMT and cf-PWV values of individuals drinking > 70 g/wk were higher than those of the reference group (nondrinkers) by 0.02 mm (p = 0.030) and 0.42 m/s (p = 0.021), respectively. The association between alcohol consumption with vascular structure and arterial stiffness only attains statistical significance for cf-PWV (p = 0.039) and c-IMT (p = 0.019), showing an association which suggests a J-shaped association. This association was not statistically significant for ba-PWV and CAVI (p = 0.446 and p = 0.141, respectively), although a similar trend was observed with ba-PWV. CONCLUSIONS: The results of this study suggest that heavy alcohol consumption (>70 g/wk) is associated with increased c-IMT and cf-PWV. Moreover, we found a J-shaped association between alcohol consumption and c-IMT and cf-PWV values as markers of vascular structure and arterial stiffness, with no association with ba-PWV and CAVI being observed.

Time to Surgery Reduction in Hip Fracture Patients on an Integrated Orthogeriatric Unit: A Comparative Study of Three Healthcare Models.

OBJECTIVE: To investigate the clinical efficacy of three different healthcare models (Traditional Model, Geriatric Consultant Model, and Orthogeriatric Unit Model) consecutively applied to a single academic center (University Hospital of Salamanca, Spain) for older hip fracture patients. METHODS: We performed a retrospective study, including 2741 hip fracture patients older than 64 years, admitted between 1 January 2003 and 31 December 2014 to the University Hospital of Salamanca. Patients were divided into three groups according to the healthcare model applied. There were 983 patients on the Traditional Model, 945 patients on the Geriatric Consultant Model, and 813 patients on the Orthogeriatric Unit Model. We recorded age and gender of patients, functional status at admission (Barthel Index, Katz Index, and Physical Red Cross Scale), type of fracture, and intervention, and we analyzed the length of stay, time to surgery, post-surgical stay, and in-hospital mortality according to the healthcare model applied. RESULTS: Hip fractures are much more frequent in women, and an increase in the average age of patients was observed along with the study (P < 0.001). The most common type of fracture in the three models studied was an extracapsular fracture, for which the most common surgical procedure used was osteosynthesis. On the functional status of patients, there were no differences on the ambulatory ability previous to fracture, measured by the Physical Red Cross Scale, and the percentage of patients with a slight dependence determined by the Barthel Index (>60) was similar in both groups, but considering the Katz Index, the percentage of patients with a high degree of independence (A-B) was significantly higher for the group of patients treated on the Orthogeriatric Unit Model period (56%, P = 0.009). The Orthogeriatric Unit Model registered the greatest percentage of patients undergoing surgery (96.1%, P < 0.001) and the greatest number of early surgical procedures (<24 h) (24.8%, P < 0.001). The orthogeriatric unit model showed the shortest duration of stay (9 days median), decreasing by one day in respect of each of the other models studied (P < 0.001). Time to surgery was also significantly reduced with the Orthogeriatric Unit Model (median of 3 days, P < 0.001). With regard to in-hospital follow-up, there was a reduction in in-hospital mortality during the study period. We observed differences among the three healthcare models, but without statistical significance. CONCLUSIONS: The healthcare model based on an Orthogeriatric Unit seems to be the most efficient, because it reaches a reduction in time to surgery, with an increased number of patients surgically treated on in the first 24 h, and the greatest frequency of surgically-treated patients.

Vascular and cognitive effects of cocoa-rich chocolate in postmenopausal women: a study protocol for a randomised clinical trial.

INTRODUCTION: The intake of polyphenols has certain health benefits. This study will aim to assess the effect of adding a daily amount of chocolate high in cocoa content and polyphenols to the normal diet on blood pressure, vascular function, cognitive performance, quality of life and body composition in postmenopausal women. METHODS AND ANALYSIS: Here we plan a randomised clinical trial with two parallel groups involving a total of 140 women between 50 and 64 years in the postmenopausal period, defined by amenorrhoea of ​​at least 12 consecutive months. The main variable will be the change in blood pressure. Secondary variables will be changes in vascular function, quality of life, cognitive performance and body composition. The intervention group will be given chocolate containing 99% cocoa, with instructions to add 10 g daily to their normal diet for 6 months. The daily nutritional contribution of this amount of chocolate is 59 kcal and 65.4 mg of polyphenols. There will be no intervention in the control group. All variables will be measured at the baseline visit and 3 and 6 months after randomisation, except cognitive performance and quality of life, which will only be assessed at baseline and at 6 months. Recruitment is scheduled to begin on 1 June 2018, and the study will continue until 31 May 2019. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Ethics Committee of the Health Area of Salamanca, Spain ('CREC of Health Area of Salamanca'), in February 2018. A SPIRIT checklist is available for this protocol. The clinical trial has been registered at ClinicalTrials.gov provided by the US National Library of Medicine, number NCT03492983. The results will be disseminated through open access peer-reviewed journals, conference presentations, broadcast media and a presentation to stakeholders.

Effectiveness of an intensive intervention to improve lifestyles in people with intermediate cardiovascular risk (DATE study): Study protocol for a randomized controlled trial.

AIM: The aim of this study was to evaluate the effectiveness of an intensive intervention led by primary care nurses for lifestyle modification among people with intermediate cardiovascular risk. BACKGROUND: Cardiovascular diseases may be prevented by adopting healthy lifestyles. Interventions focused on populations at risk are more efficient than those aimed at the general population. More than 50 per cent of cardiovascular events occur in people with intermediate cardiovascular risk, but only a few studies have targeted this population. DESIGN: A randomized controlled trial approved in January 2017. METHODS: We will recruit 208 participants aged 35-74 years who have intermediate cardiovascular risk. They will be selected by consecutive sampling and will be randomized into a control group or intervention group. Individual standardized brief counselling on healthy lifestyles will be provided to both groups. Additionally, individuals from the intervention group will receive four weekly group sessions focusing on cardiovascular risk, healthy diet, moderation in alcohol consumption, daily physical activity, stress management and smoking cessation and two motivational follow-up calls. The primary outcome will be the lifestyle modification measured by total steps recorded by a pedometer, total score on the Mediterranean Diet Adherence Screener and percentage of current smokers. DISCUSSION: This study will allow us to investigate whether an intensive intervention based on a multifactorial group approach is more effective in lifestyle modification than individual standardized brief counseling among adults with intermediate cardiovascular risk. Our results could lead to the establishment of new strategies for cardiovascular risk management.

Remarkably higher efficacy and a wider safety window for nonfrontline over first-line drug combinations in the adenocarcinoma Colo 320DM cell line.

PURPOSE: To determine in vitro, the efficacy and safety window of not-front-line and first-line anti-colorectal (CRC) drug combinations. METHODS: The adenocarcinoma cell line Colo 320DM and normal human mesenchymal stem cells derived from adipose tissue were used respectively to determine the anti-CRC efficacy (% of Colo 320DM cell death [CD]) and safety window [SW] - % Colo 320DM percent cancer death (PCD)/% of mesenchymal stem cell's death) of drug combinations, using the adenosine triphosphate-based chemotherapy response assay (ATP-CRA). RESULTS: First-line anti-CRC drug combinations (5-fluorouracil [5FU]/oxaliplatin [oxa] and 5-FU/Oxa /leucovorin [Leuco]) produced 57.7% and 52.4% CD, and 1.38 and 2.44 SW, respectively. Combinations of 5-FU/Oxa and 1 to 3 non-front line drugs led to 56.3-99.8% CD and to 0.96-2.2 SW. The highest safety window corresponded to 5FU/Oxa/ carboplatin [Carbo] (93% CD and 1.4 SW) and to 5-FU/ Oxa/cisplatin [Cispl] (93.5% CD and 1.4 SW). In contrast, non-front line drugs led to 89.8-97.4% CD and to 1.1-78.2 SW. Outstandingly, those combinations containing Carbo/ Cispl/3,3'-diindolylmethane (DIM), aspirin (Asp), or 3,3'- DIM/ Asp showed a very high CD (91.9-96.9% [39.2-39.5 times higher than first-line-combined drugs]) and very wide SW (57.8-81.56 [66.6-40 times higher than the first-line drug combinations]). CONCLUSIONS: Human mesenchymal stem cells could be an excellent alternative to laboratory animals, when testing the safety profiles of drugs. The most promising combinations of non-frontline drugs to treat CRC are Carbo/Cispl/ Asp and Carbo/Cispl/DIM.

Association of VAV2 and VAV3 polymorphisms with cardiovascular risk factors.

Hypertension, diabetes and obesity are cardiovascular risk factors closely associated to the development of renal and cardiovascular target organ damage. VAV2 and VAV3, members of the VAV family proto-oncogenes, are guanosine nucleotide exchange factors for the Rho and Rac GTPase family, which is related with cardiovascular homeostasis. We have analyzed the relationship between the presence of VAV2 rs602990 and VAV3 rs7528153 polymorphisms with cardiovascular risk factors and target organ damage (heart, vessels and kidney) in 411 subjects. Our results show that being carrier of the T allele in VAV2 rs602990 polymorphism is associated with an increased risk of obesity, reduced levels of ankle-brachial index and diastolic blood pressure and reduced retinal artery caliber. In addition, being carrier of T allele is associated with increased risk of target organ damage in males. On the other hand, being carrier of the T allele in VAV3 rs7528153 polymorphism is associated with a decreased susceptibility of developing a pathologic state composed by the presence of hypertension, diabetes, obesity or cardiovascular damage, and with an increased risk of developing altered basal glycaemia. This is the first report showing an association between VAV2 and VAV3 polymorphisms with cardiovascular risk factors and target organ damage.

Short-Term Effectiveness of a Mobile Phone App for Increasing Physical Activity and Adherence to the Mediterranean Diet in Primary Care: A Randomized Controlled Trial (EVIDENT II Study).

BACKGROUND: The use of mobile phone apps for improving lifestyles has become generalized in the population, although little is still known about their effectiveness in improving health. OBJECTIVE: We evaluate the effect of adding an app to standard counseling on increased physical activity (PA) and adherence to the Mediterranean diet, 3 months after implementation. METHODS: A randomized, multicenter clinical trial was carried out. A total of 833 participants were recruited in six primary care centers in Spain through random sampling: 415 in the app+counseling group and 418 in the counseling only group. Counseling on PA and the Mediterranean diet was given to both groups. The app+counseling participants additionally received training in the use of an app designed to promote PA and the Mediterranean diet over a 3-month period. PA was measured with the 7-day Physical Activity Recall (PAR) questionnaire and an accelerometer; adherence to the Mediterranean diet was assessed using the Mediterranean Diet Adherence Screener questionnaire. RESULTS: Participants were predominantly female in both the app+counseling (249/415, 60.0%) and counseling only (268/418, 64.1%) groups, with a mean age of 51.4 (SD 12.1) and 52.3 (SD 12.0) years, respectively. Leisure-time moderate-to-vigorous physical activity (MVPA) by 7-day PAR increased in the app+counseling (mean 29, 95% CI 5-53 min/week; P=.02) but not in the counseling only group (mean 17.4, 95% CI -18 to 53 min/week; P=.38). No differences in increase of activity were found between the two groups. The accelerometer recorded a decrease in PA after 3 months in both groups: MVPA mean -55.3 (95% CI -75.8 to -34.9) min/week in app+counseling group and mean -30.1 (95% CI -51.8 to -8.4) min/week in counseling only group. Adherence to the Mediterranean diet increased in both groups (8.4% in app+counseling and 10.4% in counseling only group), with an increase in score of 0.42 and 0.53 points, respectively (P<.001), but no difference between groups (P=.86). CONCLUSIONS: Leisure-time MVPA increased more in the app+counseling than counseling only group, although no difference was found when comparing the increase between the two groups. Counseling accompanied by printed materials appears to be effective in improving adherence to the Mediterranean diet, although the app does not increase adherence. CLINICALTRIAL: Clinicaltrials.gov NCT02016014; https://clinicaltrials.gov/ct2/show/NCT02016014 (Archived by WebCite at http://www.webcitation.org/6mnopADbf).

Association between different risk factors and vascular accelerated ageing (EVA study): study protocol for a cross-sectional, descriptive observational study.

INTRODUCTION: The process of population ageing that is occurring in developed societies represents a major challenge for the health system. The aim of this study is to analyse factors that have an influence on early vascular ageing (EVA), estimated by carotid-femoral pulse wave velocity (cf-PWV) and Cardio Ankle Vascular Index (CAVI), and to determine differences by gender in a Spanish population. METHODS AND ANALYSIS: An observational, descriptive, cross-sectional study. STUDY POPULATION: From the population assigned to the participating healthcare centres, a cluster random sampling stratified by age and gender will be performed to obtain 500 participants aged between 35 and 75. Those who meet the inclusion criteria and give written informed consent will be included in the study. MEASUREMENTS: Main dependent variables: cf-PWV determined using the SphygmoCor System and CAVI estimated using VASERA. Secondary dependent variables: telomere length, carotid intima-media thickness, central and peripheral augmentation index, ankle-brachial pulse wave velocity, ankle-brachial index, retinal arteriovenous index, and renal and cardiac organ damage. INDEPENDENT VARIABLES: lifestyles (physical activity, adherence to the Mediterranean diet, alcohol and tobacco consumption); psychological factors (depression, anxiety and chronic stress); inflammatory factors and oxidative stress. ETHICS AND DISSEMINATION: The study has been approved by the clinical research ethics committee of the healthcare area of Salamanca. All study participants will sign an informed consent form agreeing to participate in the study in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow the understanding of the relationship of the different influencing factors and their relative weight in the development of EVA. At least 5 publications in first-quartile scientific journals are planned. TRIAL REGISTRATION NUMBER: NCT02623894; Pre-results.

Evolution of target organ damage and haemodynamic parameters over 4†years in patients with increased insulin resistance: the LOD-DIABETES prospective observational study.

OBJECTIVES: We prospectively examined the impact of type 2 diabetes compared with metabolic syndrome (MetS) on the development of vascular disease over 4 years as determined by anatomic and functional markers of vascular disease. By comparing the vascular outcomes of the 2 disorders, we seek to determine the independent effect of elevated glucose levels on vascular disease. SETTING: 2 primary care centres in Salamanca, Spain. PARTICIPANTS: We performed a prospective observational study involving 112 patients (68 with type 2 diabetes and 44 with MetS) who were followed for 4 years. PRIMARY AND SECONDARY OUTCOME MEASURES: Measurements included blood pressure, blood glucose, lipids, smoking, body mass index, waist circumference, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), hs-c-reactive protein and fibrinogen levels. We also evaluated vascular, carotid intima media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index, heart and renal target organ damage (TOD). The haemodynamic parameters were central (CAIx) and peripheral (PAIx) augmentation indices. RESULTS: In year 4, participants with type 2 diabetes had increased IMT thickness. These patients had more plaques and an IMT>0.90 mm. In participants with MetS, we only found an increase in the number of plaques. We found no changes in PWV, CAIx and PAIx. The patients with diabetes had a greater frequency of vascular TOD. There were no differences neither in renal nor cardiac percentage of TOD in the patients with MetS or diabetes mellitus type 2. CONCLUSIONS: This prospective study showed that the evolution of vascular TOD is different in participants with type 2 diabetes compared with those with MetS. While IMT and PWV increased in type 2 diabetes, these were not modified in MetS. The renal and cardiac TOD evolution, as well as the PAIx and CAIx, did not change in either group. TRIAL REGISTRATION NUMBER: NCT01065155; Results.